Regulation of haptoglobin secretion by recombinant bovine cytokines in primary cultured bovine hepatocytes.

We examined the regulation of haptoglobin (Hp) secretion in primary cultured bovine hepatocytes using recombinant bovine (rb) proinflammatory cytokines. The concentrations of Hp in the supernatant of cultured hepatocytes after incubation with rb interleukin (IL)-6, rb tumor necrosis factor (TNF)-alpha, rbIL-1 beta or rbIFN-gamma alone or with combinations of two of these cytokines were measured by ELISA. The rbIL-6, rbTNF-alpha and rbIL-1 beta increased Hp synthesis, but rbIFN-gamma did not, and rbIL-6 was the most effective Hp inducer among these cytokines. The Hp secretion was accelerated synergistically by combined treatment with rbIL-6 and rbTNF-alpha, whereas it remained unchanged with a combination of rbIL-6 and rbIL-1 beta. In contrast, the combination of rbIL-6 and rbIFN-gamma downregulated Hp secretion. In conclusion, IL-6 is the principal cytokine in Hp secretion in bovine hepatocytes in vitro, and its activity may be regulated by other cytokines.